How a small molecule can induce UV-free tanning

Many of us know that ultraviolet rays are damaging for the skin, so as the hottest months of summer approach, a lot of us are stocking up on sunscreen and hoping for a beautiful, radiation-free tan. But what if we could get a darker skin tone without any of the risks? New research investigates.

In the United States, skin cancer is the most prevalent form of cancer. The Centers for Disease Control and Prevention (CDC) report that in 2013, almost 72,000 people had melanomas of the skin, with some studies indicating that the number of those affected has increased in the past few years.

Ultraviolet (UV) rays and sun exposure have been suggested to cause skin cancer, and it is commonly accepted that these rays damage the skin.

Particularly in the case of fair-skinned individuals, UV exposure has been shown to significantly increase the risk of skin cancer. This happens because fair-skinned people do not produce eumelanin, which is a protective, dark pigment.

Although products such as sunscreen protect us from many of the sun's harmful radiations, the American Cancer Society caution that even the best sunscreen is not 100 percent UV-proof, allowing some of the sun's damaging rays to still get through.

New research, however, may have found a way to pigment the skin without any UV exposure.

Scientists from the Massachusetts General Hospital (MGH) and Dana-Farber Cancer Institute, both in Boston, MA, are following up on a previous study that showed the molecular pathways that are involved in tanning, and they managed to promote tanning in mice that do not normally produce eumelanin.

The lead investigator for both studies was Dr. David E. Fisher, chief of the Department of Dermatology at MGH, and the study is published in the journal Cell Reports.

Building on previous research in skin pigmentation

In their previous study, Dr. Fisher and team found that a compound called forskolin could induce tanning in a strand of "red-haired mice" that had been genetically modified to be unable to tan.

These mice had a gene variation that interfered with the molecular pathway that causes the skin to produce melanin, which is the pigment that gives skin its color.

Further down the molecular pathway, forskolin activated another protein responsible for pigmentation and induced the production of eumelanin in mice.

However, in humans, the same compound was not successful. The researchers suspect that this was because human skin is so much thicker than mouse skin. Now, in the new study, Dr. Fisher and team tried a different way to artificially darken human skin.

Previous studies referenced by Dr. Fisher and team showed that inhibiting the action of certain enzymes can induce pigmentation in mice. These enzymes are called salt-inducible kinases (SIKs).

In this context, for the new study, Dr. Fisher and colleagues set out to darken human skin by inhibiting the same SIKs.

New class of small, SIK-inhibiting molecules induces tanning in human skin

The team created a class of SIK-inhibiting molecules specially designed to better penetrate human skin. These molecules weighed less and had greater ability to dissolve and permeate through the membrane's lipids, meaning that they had a higher "lipid solubility."

Dr. Fisher and his team tested the molecules in a laboratory culture of human skin and discovered that the more molecules they applied, the more the skin darkened. The artificially induced tan lasted for several days.

Additionally, when the researchers applied a stronger dose of these molecules to the skin of red-haired mice, they turned almost completely black in 1 to 2 days. The artificial tan wore off after a few days, as skin cells normally renew themselves.

Dr. Fisher comments on these findings:

"The activation of the tanning/pigmentation pathway by this new class of small molecules is physiologically identical to UV-induced pigmentation without the DNA-damaging effects of UV. We need to conduct safety studies, which are always essential with potential new treatment compounds, and better understand the actions of these agents."

In the long-term, the team hopes to come up with a compound that could be used together with regular sunscreen. In the near future, the team aims to carry out toxicity studies in animals, before moving on to test in humans.

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